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Chimeric antigen receptor (CAR) T-cell therapy is rapidly advancing, offering promising treatments for patients with hematological malignancy. However, associated infectious complications remain a significant concern because of their contribution to patient morbidity and non-relapse mortality. Recent epidemiological insights shed light on risk factors for infections after CAR T-cell therapy. However, the available evidence is predominantly retrospective, highlighting a need for further prospective studies. Institutions are challenged with managing infections after CAR T-cell therapy but variations in the approaches taken underscore the importance of standardizing infection prevention and management protocols across different healthcare settings. Therefore, the Infectious Diseases Special Interest Group of the American Society of Transplantation and Cellular Therapy assembled an expert panel to develop best practice considerations. The aim was to guide healthcare professionals in optimizing infection prevention and management for CAR T-cell therapy recipients and advocates for early consultation of Infectious Diseases during treatment planning phases given the complexities involved. By synthesizing current evidence and expert opinion these best practice considerations provide the basis for understanding infection risk after CAR T-cell therapies and propose risk-mitigating strategies in children, adolescents, and adults. Continued research and collaboration will be essential to refining and effectively implementing these recommendations., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: In November 2020, the FDA issued an emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild-to-moderate COVID-19 at high risk for disease progression., Methods: We retrospectively reviewed 38 adult hematology patients who received mAbs from 11/2020 to 2/2021., Results: Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab-imdevimab. Four (11%) patients were hospitalized due to COVID-19, two (5%) progressed to severe disease and one patient (3%) died within 30 days from COVID-19 disease. Most patients (n = 34, 89%) ultimately tested negative for SARS-CoV-2, with 34% (n = 13) clearing the virus within 14 days after mAb infusion. The median time to clearance of viral shedding was 25.5 days (range: 7-138). After mAb infusion, most patients with hematological malignancies (HM) (n = 10/15; 67%) resumed therapy for underlying disease with a median delay of 21.5 days (range: 12-42). We observed a significant difference in hospitalization among patients who received a HCT versus non-HCT (0% n = 0/26 and 36% n = 4/11, respectively; p < 0.01)., Conclusions: This study demonstrates that SARS-CoV-2 specific mAb was safe and may reduce hospitalization compared to what is reported in malignant hematology patients at high risk for disease progression. Our HCT cohort patients had less hospitalization rate compared with HM cohort patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Primary objective is to evaluate safety of isavuconazonium sulfate (ISA) in pediatrics below 18 years old. Exploratory endpoint includes mortality due to probable and proven invasive fungal infection (IFI) and overall morality in this population., Patients and Methods: Retrospective review of patients below 18 years receiving ISA for ≥7 days for possible, probable, or proven IFI or prophylaxis between June 2015 and March 2018. Descriptive analysis performed to calculate median, frequency, and percentages., Results: Safety analysis included 18 patients and a subgroup of 11/18 patients were assessed for efficacy. Median age 12.5 years (4 to 17 y), median weight 50.25 kg (19 to 118 kg), 50% male, 77% acute leukemias, 94% hematopoietic cell transplant recipients, 50% matched unrelated donors and 78% in remission. Elevated alanine aminotransferase 3 times baseline within 30 days of ISA occurred in 22% (4/18). No patients had elevated bilirubin or increase in serum creatinine. All-cause mortality at 90 days was 22% (4/18) and 27% (3/11) in patients with probable or proven IFI. Clinical response rates: 14-day: 45% (5/11) partial, 27% (3/11) stable; 30-day: 45% (5/11) partial, 36% (4/11) stable; 90-day: 54% (6/11) had either partial (n=3) or complete (n=3) response to ISA., Conclusions: ISA is safe in pediatric patients for the treatment of IFI. Prospective, randomized controlled trials are warranted to determine efficacy and safety of ISA in pediatric patients with hematologic malignancies and hematopoietic cell transplant.

Allogeneic hematopoietic stem cell transplantation (alloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those who are 70 years or older are limited, and no standard conditioning regimen has been established for this population. In this retrospective study we evaluated the outcome of 53 consecutive patients aged 70 years and older who underwent alloHCT with melphalan-based reduced-intensity conditioning (RIC) at City of Hope. Engraftment was prompt, with median time to neutrophil engraftment of 15 days. More than 95% of patients achieved complete donor chimerism within 6 weeks from HCT, consistent with the "semiablative" nature of this regimen. With a median follow-up of 31.1 months, the 2-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) were 68.9%, 63.8%, and 17.0%, respectively. Cumulative incidence of relapse at 1 and 2 years was 17.0% and 19.3%, respectively. One hundred-day cumulative incidence of grades II to IV acute graft-versus-host disease was 37.7% (grades III to IV, 18.9%), and 2-year cumulative incidence of chronic graft-versus-host disease was 61.9% (extensive, 45.9%). The only significant predictor for poor OS was high/very high disease risk index. Transplant-related complications and morbidities observed here did not differ from the commonly expected in younger patients treated with RIC. In conclusion, alloHCT with a melphalan-based conditioning regimen is associated with acceptable toxicities and NRM, lower incidence of relapse, and favorable OS and PFS in patients aged 70 years or older., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)